Maternal plasma DHA levels increase prior to 29 days post-LH surge in women undergoing frozen embryo transfer: a prospective, observational study of human pregnancy

Context: Docosahexaenoic acid (DHA) is an important fatty acid required for neurological development but its importance during early fetal neurological organogenesis is unknown. Objective: To assess plasma fatty acid changes in early pregnancy in women undergoing natural cycle-frozen embryo transfer as a means of achieving accurately-timed periconceptual sampling. Design: Women undergoing frozen embryo transfer were recruited and serial fasting blood samples were taken pre-luteinising hormone (LH) surge, and at days 18, 29 and 45 post-LH surge and fatty acids were analysed using gas chromatography. Setting: Assisted Conception Unit, Glasgow Royal Infirmary, Scotland Main outcome measures: Plasma fatty acid concentrations, influence of twin pregnancies on DHA plasma concentration. Results: In pregnant women, there was a rapid, early increase in the maternal rate of change of plasma DHA concentration observed by 29 days post-LH surge (mean±SD, from 0.1±1.3 to 1.6±2.9 nmol DHA per mL plasma per day). This early pressure to increase plasma DHA concentration was further emphasised in twin pregnancies where the increase in DHA concentration over 45 days was two-fold higher than in singleton pregnancies (mean±SD increase, 74±39 nmol/mL versus 36±40 nmol/mL). An index of delta-6 desaturase activity increased 30% and positively correlated with the rate of change of DHA concentration between day 18 and 29-post LH surge (R-squared adjusted = 41%, P=0.0002). DHA was the only fatty acid with a continual accelerated increase in plasma concentration and a positive incremental area under the curve (mean±SD, 632±911 nmol/mL x day) over the first 45 days of gestation. Conclusions: An increase in maternal plasma DHA concentration is initiated in human pregnancy prior to neural tube closure which occurs at 28 days' gestation

The Large GTPase Dynamin Associates with the Spindle Midzone and Is Required for Cytokinesis

AbstractCytokinesis involves the concerted efforts of the microtubule and actin cytoskeletons as well as vesicle trafficking and membrane remodeling to form the cleavage furrow and complete daughter cell separation (for reviews, see [1–6]). The exact mechanisms that support membrane remodeling during cytokinesis remain largely undefined. In this study, we report that the large GTPase dynamin, a protein involved in membrane tubulation and vesiculation [7, 8], is essential for successful cytokinesis. Using biochemical and morphological methods, we demonstrate that dynamin localizes to the spindle midzone and the subsequent intercellular bridge in mammalian cells and is also enriched in spindle midbody extracts. In Caenorhabditis elegans, dynamin localized to newly formed cleavage furrow membranes and accumulated at the midbody of dividing embryos in a manner similar to dynamin localization in mammalian cells. Further, dynamin function appears necessary for cytokinesis, as C. elegans embryos from a dyn-1 ts strain [9], as well as dynamin RNAi-treated embryos, showed a marked defect in the late stages of cytokinesis. These findings indicate that, during mitosis, conventional dynamin is recruited to the spindle midzone and the subsequent intercellular bridge, where it plays an essential role in the final separation of dividing cells

The burden of proof: the current state of atrial fibrillation prevention and treatment trials

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015

Keeping the Promise of Community-Based Participatory Research: Integrating Applied Critical Rhetorical Methods to Amplify the Community’s Voice for Trial Development

Community-based participatory research (CBPR) represents an important improvement in the integration of marginalized voices into research programs by including community members in the designs, conduct, and dissemination of studies. CBPR often features a social justice component, generating studies designed to reduce societal disparities and improve outcomes for disenfranchised groups. However, the practical implementation of CBPR usually fails to capitalize on this promise, using the same traditional research methodologies, leadership structures, trial designs, and research questions that inculcate researcher bias. In response to the problem, we propose a new solution: Applied critical rhetorical research (ACRR) integrated into the CBPR approach to clinical health research. ACRR research combines critical/cultural studies and rhetorical methods to amplify the figurative voice of marginalized populations. ACRR can expose how majority power (i.e., hegemony) manifests in social institutions like healthcare and government, where its meanings and subjectivities are absorbed. ACRR analyses enhance CBPR by shaping research in directions that reduce stigma, unintended disenfranchisement, and culturally bound bias, increasing the yield from CBPR for researchers and the community

The Rise of Transgender and Gender Diverse Representation in the Media: Impacts on the Population

In recent years, the transgender and gender diverse (TGD) population has gained a stronger voice in the media. Although these voices are being heard, there are limits on the types of TGD representation displayed in media. The current study interviewed 27 TGD individuals. These interviews exposed how participants view the rise of TGD media representation. The main themes that emerged were TGD awareness and TGD identity discovery and role modeling. Clearly, there is a disconnect between transnormativity in the media and transnormativity in reality

Pre-conception maternal erythrocyte saturated to unsaturated fatty acid ratio predicts pregnancy after natural cycle frozen embryo transfer

The environment for embryo implantation and fetal growth and development is affected by maternal nutritional, metabolic and health status. The aim of this prospective, cohort study was to test whether plasma metabolic and inflammatory biomarkers can predict pregnancy resulting from in vitro fertilisation (IVF). Women with a natural menstrual cycle undergoing frozen embryo transfer (FET) were recruited and fasting baseline blood samples were collected a mean of 3.4 days prior to the luteinising hormone (LH) surge and a non-fasting blood sample was taken on the day of FET. Ongoing pregnancy was defined by positive fetal heartbeat on ultrasound scan at day 45 post LH surge. Thirty-six pregnancies resulted from FET in 143 women. In an overall stepwise multivariable analysis, erythrocyte saturated to unsaturated fatty acid ratio was positively associated with ongoing pregnancy. A similar model incorporating day of FET covariates found that erythrocyte saturated to unsaturated fatty acid ratio, erythrocyte fatty acid average chain length and plasma log-triglycerides predicted ongoing pregnancy. In conclusion, a higher peri-conceptional saturated to unsaturated fatty acid ratio predicted ongoing pregnancy after natural cycle frozen embryo transfer and may reflect a maternal nutritional status that facilitates pregnancy success in this assisted conception scenario

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Estimating the effects of stressors on the health, survival and reproduction of a critically endangered, long-lived species

Funding: Office of Naval Research (Grant Number(s): N000142012697, N000142112096); Strategic Environmental Research and Development Program (Grant Number(s): RC20-1097, RC20-7188, RC21-3091).Quantifying the cumulative effects of stressors on individuals and populations can inform the development of effective management and conservation strategies. We developed a Bayesian state–space model to assess the effects of multiple stressors on individual survival and reproduction. In the model, stressor effects on vital rates are mediated by changes in underlying health, allowing for the comparison of effect sizes while accounting for intrinsic factors that might affect an individual's vulnerability and resilience. We applied the model to a 50-year dataset of sightings, calving events and stressor exposure of critically endangered North Atlantic right whales Eubalaena glacialis. The viability of this population is threatened by a complex set of stressors, including vessel strikes, entanglement in fishing gear and fluctuating prey availability. We estimated that blunt and deep vessel strike injuries and severe entanglement injuries had the largest effect on the health of exposed individuals, reinforcing the urgent need for mitigation measures. Prey abundance had a smaller but protracted effect on health across individuals, and estimated long-term trends in survival and reproduction followed the trend of the prey index, highlighting that long-term ecosystem-based management strategies are also required. Our approach can be applied to quantify the effects of multiple stressors on any long-lived species where suitable indicators of health and long-term monitoring data are available.Publisher PDFPeer reviewe